A long-term objective of this proposed research is to test the hypothesis that the phenotype and function of skeletal muscle macrophages influence muscle cellular events important for the recovery of exercise-injured muscle. The specific aims are to 1) identify the phenotype of macrophage subpopulations present during the recovery of exercise-injured muscle, 2) characterize the functional heterogeneity of these macrophage subpopulations, and 3) determine if macrophage-stimulating factors regulate macrophage cytokine production. An experimental exercise model of skeletal muscle injury, eccentric muscle contractions, in which reparative mechanisms are activated, will be used. Eccentric contractions will be induced in the plantarflexor muscles, the soleus, plantaris, and gastrocnemius, of 66 male and 66 female adult C57BL/6J mice and then allowed to resume normal physical activity for 0 hours, 6 hours, and 2, 4, 7, and 14 days. Sixty additional mice will serve as untreated controls. The soleus muscle will be removed and prepared for morphological analysis to identify and quantify the specific macrophage maturational state and macrophage expression of the cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-alpha (TNF), at the midportion and proximal terminal muscle regions. The plantarflexor muscles will be removed at each of the 6 recovery time points and prepared using cell culture techniques to isolate muscle macrophages for in vitro functional studies of IL-1 and TNF production. Findings from this research may contribute to achieving a second long-term objective, the identification of nursing interventions for managing fatigue.